The objectives of this research are to investigate developmental factors on the influence of the toxicity of drugs during the perinatal period and to develop animal models for preclinical toxicologic investigation of drugs that may be administered to premature and newborn infants. Specific goals for the current year are 1) to correlate the concentration and distribution of injected bilirubin with bilirubin toxicity in newborn Gunn rats, 2) to examine the possible effect of hyperbilirubinemia on the decreased rate of hepatic glucuronidation of p-nitrophenol in Gunn rats, 3) to develop an ultramicron method for measuring unbound bilirubin in plasma or serum and 4) to investigate the mechanism of orotic acid on decrease in plasma bilirubin concentration.